Figure 1.

Immune checkpoint inhibitors induce tumour cell death by activating pre-existing CD8⁺ TILs. CD8⁺ TILs express T cell receptors (TCRs) that recognise antigens presented by major histocompatibility complexes (MHCs) on either tumour cells or antigen-presenting cells (APCs). TCR–antigen–MHC interactions prime and activate CD8⁺ TILs to induce apoptosis. This interaction, however, is downregulated by the activation of immune checkpoints, for example, the binding of cell surface receptor proteins PD-L1 (programmed death-ligand 1) with PD-1 (programmed death-1), and CTLA-4 (cytotoxic T lymphocyte-associated antigen-4) with B7 proteins. The blockade of these axes, via ICIs, allows CD8⁺ TILs to circumvent these inhibitory signals.